A RATIONAL THERAPY FOR HUMAN IMMUNODEFICIENCY VIRUS (HIV)
(C)1994 Alan M. Schwartz
Male homosexuals and intravenous drug abusers are prolific
modalities for the planet-wide spread of HIV. HIV is an RNA
retro-virus. It identifies its target white blood cell through
surface protein markers, enters the cell, sheds its protein coats
and releases two strands of viral RNA. Said RNA strands via
viral reverse transcriptase are retro-translated to DNA (with
poor fidelity, averaging one mutation per transcription) which
attaches to the human genome. The viral DNA then goes about
manufacturing hundreds of copies of new viral RNA and capsid
proteins to assemble new HIV viruses to continue the infection.
Drug efforts to intercept metabolism unique to viral reverse
transcription, e.g. AZT, perform poorly and deliver potentially
fatal side effects. They afford no prophylaxis. Efforts to
create dead viral or synthetic viral protein vaccines have been
fruitless - the remarkable HIV mutation rate evolves it beyond
immune system grasp . Live but attenuated vaccines (due to
defective viral genes) may afford significant protection at the
costs of having your genome modified by the attachment of viral
DNA, and risking spontaneous mutation back to lethality. Chicken
pox (herpes zoster) also integrates into (nerve) cell DNA to
award the host with the disease shingles in later life. Any
shingles sufferer will tell you the side effects of so obtained
chicken pox immunity are gruesome.
Billions of dollars have been porkbarrelled into AIDS research so
that infected drug addicts may one day sustain a longer and more
satisfying life. Let us consider another pathogenic scourge that
was solved not by attempts at cure, but by rational treatment.
The cholera vibrio secretes a toxin which inactivates sodium-
dependent ATPase in the intestinal lining. Said enzyme drives
active transport of water from concentrated gut contents to
dilute blood. Cholera elicits a week of massive diarrhea -
gallons of liquid feces daily - spreading the disease and killing
the host by dehydration. The only way to recover the enzyme is
to regrow the intestinal lining. The singularly effective
cholera treatment is to pour gallons of physiological saline
supplemented with 5% dextrose down the sufferer's throat.
Passive water diffusion keeps him hydrated while the bacteria are
flushed away and the enzyme is replenished. Let us consider HIV.
Nucleic acids, RNA and DNA, encode information in their base
sequence. Said rungs of the helix or double helix ladders are
supported from a scaffolding of alternating sugar-phosphate
polyester. The negative charges from each ionized phosphate
group make nucleic acids unable to easily penetrate cell and
nuclear membranes. A suite of enzymes, nucleases, is devoted to
destroying errant nucleic acids.
It is an accomplished task to synthesize said information-
encoding base sequences supported by an uncharged protein
scaffold of linear poly[N-(2-aminoethyl)]glycine. The products
are called "peptide nucleic acids." Peptide nucleic acids are
uncharged and thus readily penetrate cell and nuclear membranes.
They are unaffected by abundant and reactive cellular nucleases.
They bind to complimentary DNA or RNA sequences much more avidly
than native nucleic acid sequences, which makes the local product
unable to support transcription. The genes so bound are thus
selectively turned off and so functionally deleted.
A 17-base sequence is sufficiently long to uniquely identify any
gene in the human genome (constituting seven linear feet of DNA
molecule were it all unraveled and stretched out). Automated
synthesis of a 17-base sequence of peptide nucleic acid in
milligram amounts requires about 24 hours from its vendor
Biosearch (subsidiary of Millipore Corp.).
An effective treatment for HIV is thus evident.
Identify a vital gene or three within both viral RNA and human
genome-integrated viral DNA sequences. Synthesize complimentary
peptide nucleic acid sufficiently long, 17 base pairs or more,
that both exquisite selectivity is achieved and one or two base
pair mismatches are irrelevant. Administer periodic doses
intravenously. The HIV virus and its genome-integrated reverse
transcribed DNA will be inactivated. This is not a cure, but it
will stop the disease process and disease transmission cold.
All we can do is wait for the infected to die off naturally. The
folly of not having enacted draconian national quarantine
procedures when a readily transmissible, lethal and incurable
disease was first recognized will cost us dearly. HIV is the
first political disease, courtesy of the Gay Rights Movement.
Biology takes no notice of political expediency. Dead is dead.